Each of our Project Leaders maintains a commitment to share available research data through a variety of existing mechanisms: published papers, lectures, and presentations to the public are a few examples of this commitment. In addition, the SCDC PS-OC will develop and incorporate the following: Seminar Series In order to increase the pool of interested students and faculty, we will sponsor a regular seminar series to bring outside experts to MIT to present their research and ideas and meet with faculty and students. We have found this to be a very valuable mechanism for exploring possible new relationships. For example, this mechanism has been instrumental in expanding membership of the MIT Koch Institute for Integrative Cancer Research. This is a very effective form of outreach to increase the interest and involvement of faculty from diverse disciplines. Because of the interdisciplinary nature of this program, it is essential to have mechanisms in place to foster interactions among participants and to ensure exposure to role models active at the interfaces of physics, engineering, and cancer biology. Accordingly we plan to establish a regular seminar series which will bring in outside experts, including members of other PS-OCs, for 1-2 day visits, which would include a public seminar as well as meetings with involved faculty and, particulariy, with trainees. Website The center will maintain a website to disseminate techniques and applications. This website will allow us to share links to recently published PS-OC papers, information about our Project Leaders and their research areas, and lectures, events, and other forums of interest to those involved with the PS-OC. We will also provide links to the facilities services available at the Koch Institute. The faculty and students will use it as a one-stop resource for information about current activities and opportunities available across the PS-OC. Additionally, we anticipate using the website as a primary source of information for other NCI supported PSOCs. Trans-Network Collaborations We anticipate developing new collaborative research opportunities with other NCI-supported PS-OC's. One important advantage of having Project Leaders at institutions across the United States is that they will be able to develop new collaborations with the NCI-supported PS-OC's closest to them and with the overiay of internet technologies, the worid is open to us. We see this as an integral part of our plan to share expertise and resources with other PS-OC's while protecting research in progress. Collaborative projects with the most promise will be supported as Pilot Projects, upon the recommendation and approval of the CAC. We expect these projects to arise from activities around NCI-sponsored conferences, the ongoing work and publications of Project Leaders, and based on activities with external experts. With the support of MIT's Technology Licensing Office, reagents developed by the members of our PS-OC will be made available for license by other NCI-supported PS-OC's. Trans-Network Projects One potent mediator for setting up for collaborations between PS-OCs will be technology transfer. In addition to our work with the PS-OC Steering Committee on identifying trans-network projects, the SCDC PS-OC will develop novel technology platforms that will be generally applicable to many experimental systems in cancer biology. In particular the RNA counting technique mastered by the van Oudenaarden lab and the suspended microchannel resonant (SMR) mass sensor developed by the Manalis lab will likely be useful technologies for other PS-OCs. Below we outline concrete strategies that we will pursue to establish successful and longlasting collaborations with other PS-OCs within the network. Three of the four projects of this application will use the RNA counting technology. Based on the research proposals of these projects we estimate to design, synthesize, and characterize about SO probe libraries in the eariy phase of the projects. These probe libraries will be used in Project 1, 2, and 3 both in murine and human cells and tissue to detect single endogenous mRNA molecules. For example, some of these libraries will detect mRNAs described from the popular oncogene c-myc, tumor suppressor gene p53, several RAS genes, the paired box genes PAX3, PAX4, PAX6 and PAX7, and the DNA methyl transferases DNMT3a and DNMTSb. We will make all the libraries freely available to all PS-OCs. The library design, ordering, labeling and testing will be performed by our single-cell mRNA counting core. Moreover, we will use our budget for trans-network projects to finance synthesis of additional libraries, which are not utilized any of our projects, but will help projects in other PS-OCs fonward. We are convinced that the single molecule RNA detection will be useful for many projects in the other PS-OCs since it is very general technique which allows quantification of absolute transcription levels in the in vivo context. Since the publication of the technique the van Oudenaarden lab received many request from laboratories to apply the technique to their particular model system. We expect a similar situation when we would make our single-cell mRNA counting core available to members of the other PS-OCs.